Obiettivo
The mechanisms of the immune and endocrine cell interaction within the islet and resulting β-cell death are
highly complex and largely unknown. To investigate the cellular crosstalk in the pancreas and how its
disturbance leads to insufficient insulin production is important to understand the pathology of the disease. This
is the major goal of this project.
Activation of inflammation is not only a trigger for β-cell destruction, but also a major factor for the metabolic
syndrome, including insulin resistance and complications of diabetes.
Signalling and activation of immune cells is facilitated by secreted pro-inflammatory stimulators and via cell-cell
interactions. I propose that a group of adhesion and signalling molecules, the Siglecs (sialic acid–binding
immunoglobulin (Ig)-like lectins) mediate such interactions. They are responsible for immune system activation
and have been initially found in cells of hematopoietic origin. I made the groundbreaking observation of cell
type specific Siglec expression in the human pancreas: Siglecs were differentially expressed in glucagon
producing α-cells, and in insulin producing β-cells. A diabetic milieu had an inductive effect on Siglec
expression in the α-cells, but lead to decreased β-cell specific Siglecs. This loss of Siglecs in the β-cell could be
detrimental and result in an excessive cytokine release and in turn switches on Siglec responses in neighbouring
cells. In my proposed studies I will investigate the role of Siglecs in the cellular network in islets and in the
circulation to probe whether changes in Siglec expression are causative in the development of diabetes.
My project is a pioneer and multidisciplinary study combining the current knowledge of glycobiochemistry
and β-cell biology in diabetes. The project uses multi-model cell systems of healthy and diseased human
pancreatic tissue, isolated human islets, isolated human β-cells as well as diabetic mouse models, all of them
being absolutely novel and high-risk to a large extend.
Campo scientifico
- natural sciencesbiological sciencescell biology
- medical and health sciencesclinical medicineendocrinologydiabetes
- engineering and technologyelectrical engineering, electronic engineering, information engineeringinformation engineeringtelecommunicationstelecommunications networksmobile network
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesbasic medicinepathology
Invito a presentare proposte
ERC-2010-StG_20091118
Vedi altri progetti per questo bando
Meccanismo di finanziamento
ERC-SG - ERC Starting GrantIstituzione ospitante
28359 Bremen
Germania